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AzTrials

Acute Lymphocytic LeukemiaPhase 1/2NCT03104491

Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

A Phase 1/2 study testing Inotuzumab Ozogamicin in people with Acute Lymphocytic Leukemia, run by Leland Metheny at 7 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects. Read more about this study

Who is it for?
Ages 16 to 75 years
Conditions the study is for
Acute Lymphocytic Leukemia
What is being tested?
Inotuzumab Ozogamicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
7 sitesUnited States
Study dates
31 Jul 2017to May 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Phase 1 Inclusion Criteria
  • Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
  • Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • Patients who are between T+40 and T+100 after allogeneic transplantation. Patients must receive their first dose of inotuzumab at or before T+100.
  • Patients who have/are either:
  • Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation
Show all 58Show fewer
  • ---Pre- or Post-Transplant Minimal Residual Disease defined by:
  • ----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.
  • In second or third complete remission at the time of allogeneic transplantation
  • Treated with reduced intensity regimens or non-myeloablative conditioning regimens
  • Lymphoid blast crisis of CML
  • Are relapsed or refractory to at least 1 line of chemotherapy
  • Philadelphia-like ALL
  • Patients who have evidence of donor chimerism after allogeneic transplantation.
  • ECOG Performance status < 2
  • Participants must have ANC > 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/µL for 7 days.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Participants must have the ability to understand and the willingness to sign a written informed consent document.
  • Phase 2 Inclusion Criteria
  • Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
  • Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • Patients who are between T+40 and T+100 after allogeneic transplantation
  • Patients who have/are either:
  • Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation
  • ---Post-Transplant Minimal Residual Disease defined by:
  • ----Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.
  • In second or third complete remission at the time of allogeneic transplantation
  • Treated with reduced intensity regimens as defined per institutional standard of practice
  • Lymphoid blast crisis of CML
  • Are relapsed or refractory to at least 1 line of chemotherapy
  • Philadelphia-like ALL
  • Patients who have > 80% donor chimerism after allogeneic transplantation.
  • Philadelphia chromosome positive ALL must have failed at least 1 TKI
  • ECOG Performance status < 1
  • pre-transplant evaluation, see 10.1.1
  • Participants must have ANC > 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count > 50,000/µL for 7 days.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Participants must have the ability to understand and the willingness to sign a written informed consent document.
  • Phase 1 and 2 Exclusion Criteria:
  • Patients with clinical evidence of disease progression prior to enrollment
  • Persistent prior treatment toxicities Grade 2 and above according to NCI CTCAE Version 4.03 (with the exception for alopecia, neuropathy, etc.)
  • Patients with inadequate organ function as defined by:
  • Creatinine clearance < 30ml/min
  • Bilirubin > 2X institutional upper limit of normal
  • AST (SGOT) > 2X institutional upper limit of normal
  • ALT (SGPT) > 2X institutional upper limit of normal
  • GVHD grade III or IV (for patients with a prior allogeneic transplant).
  • Active acute or chronic GVHD of the liver (for patients with a prior allogeneic transplant)
  • History of VOD
  • Use of concomitant TKI or sirolimus
  • Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast)
  • Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breastfeeding women are excluded from this study because inotuzumab ozogamicin may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with inotuzumab ozogamicin, breastfeeding should be discontinued if the mother is treated with inotuzumab ozogamicin. These potential risks may also apply to other agents used in this study.
  • Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
  • Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
  • Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds

Who cannot join

None listed.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Leland Metheny, MD contact

1-800-641-2422

CTUReferral@UHhospitals.org

Ron Sobecks, MD contact

216-444-6833

sobeckr@ccf.org

7 sites in 1 country

United States7 sites, 4 recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Roman Shapiro, MD, Roman_Shapiro@DFCI.HARVARD.EDU

    Recruiting

  • University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

    Leland Metheny, MD, 800-641-2422, CTUReferral@UHhospitals.org

    Leland Metheny

    Recruiting

  • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

    Active, not recruiting

  • The James Cancer Hospital and Solove Research Institute

    Columbus, Ohio, 43210

    Jiasheng Wang, MD

    Jiasheng Wang, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Active, not recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68106

    Vijaya Bhatt, MD, Vijaya.bhatt@unmc.edu

    Recruiting

  • The University of Kansas Cancer Center

    Westwood, Kansas, 66205

    Active, not recruiting

Other trials in United States

About this study

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects.

The Phase II portion of this study is to see what side effects are seen with medication after transplant.

Inotuzumab ozogamicin is a combination of an antibody and chemotherapy which has been shown to have significant activity against relapsed/refractory acute lymphocytic leukemia (ALL).

Inotuzumab ozogamicin is considered experimental in this study.

Read the detailed description

Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of patients who underwent allogeneic transplantation for ALL and have a high risk of relapse. The Phase I portion of this study will be a 3+3 dose escalation trial. This is followed by a phase 2 cohort at the recommended Phase 2 dose (RP2D). Participants will receive study treatment up to 4 cycles until relapse of disease, unacceptable toxicity, or death, whichever occurs first

Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.

Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. In order to be included in the safety profile endpoint review, subjects must have received at least of 1 cycle of treatment.

Primary Objective

Phase I: To define a post hematopoietic stem cell transplantation maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of inotuzumab ozogamicin.

Phase II: To assess the efficacy of inotuzumab ozogamicin as measured by diseasefree survival (DFS) at one year.

Secondary Objective(s)

Phase I:

  • To evaluate disease-free survival (DFS), nonrelapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.
  • To determine safety profile of inotuzumab ozogamicin after transplant including the incidence of myeloid toxicity and secondary graft failure and the rate of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS).
  • To determine if inotuzumab ozogamicin at these doses is effective at eradicating minimal residual disease in this cohort of participants

Phase II:

  • To assess additional evidence of efficacy and safety as measured by non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.
  • To determine if inotuzumab ozogamicin at these doses is effective at eradicating MRD.
  • To confirm the safety profile of inotuzumab ozogamicin therapy after transplant including myeloid toxicity, secondary graft failure, and the rate of VOD/SOS.
  • To evaluate the pharmacokinetics of inotuzumab ozogamicin post allogeneic transplant
Being tested
Inotuzumab Ozogamicin
Keywords
allogeneic hematopoietic stem cell transplantation, donor chimerism
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Inotuzumab OzogamicinDrug

    Inotuzumab ozogamicin, IV, 28 day cycles

    Phase 1 dosages:

    Dose Level -2 (0.1 mg/m^2)

    Dose Level -1 (0.2 mg/m^2)

    Dose Level 0 (0.3 mg/m^2)

    Dose Level 1 (0.4 mg/m^2)

    Dose Level 2 (0.5 mg/m^2)

    Dose Level 3 (0.6 mg/m^2)

Study groups in NCT03104491
Study groupRoleWhat they receive
Inotuzumab OzogamicinExperimentalPhase I: A maximum of 4 cycles will be allowed and doses will be adjusted in 0.1mg/m2 increments using a dose escalation scale depending on tolerability. Total range of dose levels for participants is 0.1-0.6mg/m^2. Phase II: Participants will be enrolled until all Phase I participants have been followed and assessed for toxicity for at least 4 weeks after the fourth treatment dose of inotuzumab ozogamicin or 4 weeks after the participant goes off treatment, whichever comes first. Doses to be administered will be determined in the phase I portion of the study. The recommended phase 2 dose is 0.3mg/m2. Repeat cycles every 28 days for up to 4 cycles
Receives: Drug: Inotuzumab Ozogamicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I MTD

    Defined post hematopoietic stem cell transplantation MTD

    Measured: Up to 112 days (16 weeks)

  2. Phase I DLTs

    Frequency of DLTs during the first two cycles in ALL-participants

    Measured: Up to 112 days (16 weeks)

  3. Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Measured: At 3 months after initial treatment

  4. Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Measured: At 6 months after initial treatment

  5. Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Measured: At 9 months after initial treatment

  6. Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Measured: At 1 year after initial treatment

  7. Phase II Median DFS

    Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)".

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

    Measured: Post first dose of inotuzumab ozogamicin

Secondary outcomes (65)

  1. Phase I Median DFS

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 3 months after initial treatment

  2. Phase I Median DFS

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 6 months after initial treatment

  3. Phase I Median DFS

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 9 months after initial treatment

  4. Phase I Median DFS

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 1 year after initial treatment

  5. Phase I Median DFS

    Efficacy as measured by phase I DFS at one year. Estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI)

    DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)"

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  6. Phase I NRM

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 3 months after initial treatment

  7. Phase I NRM

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 6 months after initial treatment

  8. Phase I NRM

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 9 months after initial treatment

  9. Phase I NRM

    Phase I NRM, defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 1 year after initial treatment

  10. Phase I NRM

    Phase I NRM , defined as time from date of first dose to death due to any cause without prior relapse. Criteria used: For ALL, evidence of disease in the blood or bone marrow (flow cytometry or PCR).

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  11. Phase I Relapse

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 3 months after initial treatment

  12. Phase I Relapse

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 6 months after initial treatment

  13. Phase I Relapse

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 9 months after initial treatment

  14. Phase I Relapse

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 1 year after initial treatment

  15. Phase I Relapse

    Phase I relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  16. Phase I Relapse-related mortality

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 3 months after initial treatment

  17. Phase I Relapse-related mortality

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 6 months after initial treatment

  18. Phase I Relapse-related mortality

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 9 months after initial treatment

  19. Phase I Relapse-related mortality

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 1 year after initial treatment

  20. Phase I Relapse-related mortality

    Phase I Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  21. Phase I Median OS

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 3 months after initial treatment

  22. Phase I Median OS

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 6 months after initial treatment

  23. Phase I Median OS

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 9 months after initial treatment

  24. Phase I Median OS

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 1 year after initial treatment

  25. Phase I Median OS

    Phase I OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  26. Phase I Incidence of myeloid toxicity

    Number of patients who develop myeloid toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia CTCAE 4

    Measured: At 1 year

  27. Phase I Incidence of secondary graft failure

    Number of patients who develop secondary graft failure while on study, defined as:

    Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced

    Measured: At 1 year

  28. Phase I incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)

    Safety profile of intervention as measured by incidence of VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

    Measured: At 1 year

  29. Phase I rate of VOD/SOS - number of participants affected

    Safety profile of intervention as measured by number of participants affected by VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

    Measured: At 1 year

  30. Phase I - Percent of participants with grade 3 + AE/SAEs

    Phase I safety profile of intervention as measured by percent of participants with grade 3 + AE/SAEs

    Measured: At 1 year

  31. Phase II Non-relapse mortality (NRM)

    Phase II Non-relapse mortality (NRM), defined as time from date of first dose to death due to any cause without prior relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 3 months after initial treatment

  32. Phase II Relapse

    Phase II relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 6 months after initial treatment

  33. Phase II Relapse

    Phase II relapse rate, defined as time from date of first dose to the date of first relapse.

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 9 months after initial treatment

  34. Phase II Relapse-related mortality

    Phase II Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: At 1 year after initial treatment

  35. Phase II Relapse-related mortality

    Phase II Relapse-related mortality, defined time from date of first dose to death due to any cause with prior relapse

    Reported as Cumulative Incidence and 2-sided 80% CI and 2-sided 95% CI

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  36. Phase II Median OS

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 3 months after initial treatment

  37. Phase II Median OS

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 6 months after initial treatment

  38. Phase II Median OS

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 9 months after initial treatment

  39. Phase II Median OS

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: At 1 year after initial treatment

  40. Phase II Median OS

    Phase II OS, defined from time from date of first dose to death due to any cause, estimated using Kaplan-Meier, reported as median and 95% CI

    Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  41. Phase II Response Rate

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

    Measured: At 3 months after initial treatment

  42. Phase II Response Rate

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

    Measured: At 6 months after initial treatment

  43. Phase II Response Rate

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

    Measured: At 9 months after initial treatment

  44. Phase II Response Rate

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

    Measured: At 1 year after initial treatment

  45. Phase II Response Rate

    Defined as the proportion of patients with a best overall response of eradicating MRD at the time each patient discontinues treatment with Inotuzumab Ozogamicin

    Measured: Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

  46. Phase II Incidence of myeloid toxicity

    Number of patients who develop myeloid toxicity while on study, defined as grade of anemia, neutropenia and thrombocytopenia CTCAE 4

    Measured: At 1 year

  47. Phase II Incidence of secondary graft failure

    Number of patients who develop secondary graft failure while on study, defined as:

    Either cytopenias after initial engraftment (ANC <500/µL), with (a) donor chimerism of less than 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion (DLI) or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism was >5%. Exclusion criteria for diagnosis of GF were (a) disease relapse (b) graft versus host disease or (c) other causes of cytopenias such as, viral infections, or drug induced

    Measured: At 1 year after initial treatment

  48. Phase I incidence of VOD/SOS

    Safety profile of intervention as measured by incidence of VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

    Measured: At 1 year

  49. Phase II rate of VOD/SOS - number of participants affected

    Safety profile of intervention as measured by number of participants affected by VOD/SOS disease in the phase I portion of the study, defined as the occurrence of 2 of the following 3 clinical criteria:

    • Total serum bilirubin level >34 μmol/L (>2.0 mg/dL).
    • An increase in liver size from baseline or development of right upper quadrant pain of liver origin.
    • Sudden weight gain >2.5% during any 72-hour period after infusion of investigational product because of fluid accumulation or development of ascites.

    Measured: At 1 year

  50. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days)

  51. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 1 Day 1 (C1D1) after 1 hour (each cycle is 28 days)

  52. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 1 Day 1 (C1D1) after 4 hours (each cycle is 28 days)

  53. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 1 Day 7 (C1D7) (each cycle is 28 days)

  54. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days)

  55. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days)

  56. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days)

  57. Phase II pharmacokinetic (PK) parameters - Cmax

    Phase II PK parameter

    Cmax is maximum concentration. Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days)

  58. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 1 Day 1 (C1D1) after 0 hours (each cycle is 28 days)

  59. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle1 Day 1 (C1D1) after 1 hour (each cycle is 28 days)

  60. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle1 Day 1 (C1D1) after 4 hours (each cycle is 28 days)

  61. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 1 Day 7 (C1D7) (each cycle is 28 days)

  62. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 2 Day 1 (C2D1) after 0 hours (each cycle is 28 days)

  63. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 2 Day 1 (C2D1) after 1 hour (each cycle is 28 days)

  64. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 4 Day 1 (C4D1) after 0 hours (each cycle is 28 days)

  65. Phase II pharmacokinetic (PK) parameters - Ctrough

    Phase II PK parameter

    Ctrough is lowest concertration of Inotuzumab in the blood.Descriptive statistics (n, mean, SD, %CV, median, minimum, maximum, geometric mean, its associated geometric %CV) of inotuzumab ozogamicin serum concentrations will be presented in tabular form by cycle, day, and nominal time for the PK concentration analysis population.

    Measured: At Cycle 4 Day 1 (C4D1) after 1 hour (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2017
  2. Study start31 Jul 2017
  3. Primary completionNov 2026 (estimated)
  4. Study completionMay 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03104491
Sponsor's protocol ID
CASE1916
Status last verified
Sep 2026
First submitted
3 Apr 2017
Last updated
10 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.

    PubMed 41671463

  • Metheny LL, Sobecks R, Cho C, Fu P, Margevicius S, Wang J, Ciarrone L, Kopp S, Convents RD, Majhail N, Caimi PF, Otegbeye F, Cooper BW, Gallogly M, Malek E, Tomlinson B, Gerds AT, Hamilton B, Giralt S, Perales MA, de Lima M. A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia. Blood Adv. 2024 Mar 26;8(6):1384-1391. doi: 10.1182/bloodadvances.2023011514.

    PubMed 38170741

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Inotuzumab Ozogamicin in people with Acute Lymphocytic Leukemia, run by Leland Metheny at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 58 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Leland Metheny, MD (1-800-641-2422, CTUReferral@UHhospitals.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I MTD (time frame: Up to 112 days (16 weeks)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03104491, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.

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